A detailed analysis of the structue and organization of the important family of genes that encode anti-DNA autoantibodies will enhance our understanding of the role of the immunoglobulin V (variable) gene repertoire in the pathogenesis of autoimmune disease. Using a recently developed panel of anti-DNA autoantibody producing hybridomas derived from NZB/NZW F1 mice, and applying recent advances in recombinant DNA technology, I propose to: a) Clone and sequence several anti-DNA autoantibody VH and VL genes. b) Determine the number of germline VH and VL gene segments contributing to the autoimmune response. c) Determine whether polymorphisms in the germline repertoire of these genes are at all associated with the development of autoimmune disease. d) Determine the linkage relationships among the V gene segments encoding the anti-DNA autoantibodies and their location relative to other V gene loci.